Abstract
BackgroundDifferential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response.MethodsThirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Abneg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68+, CD3+, CD20+, CD21+, CD117+, and CD138+ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Abneg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations.ResultsAt study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68+ and sublining CD21+, CD20+, and CD3+ cells than Abneg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117+ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Abneg RA patients. Conversely, Abneg RA patients showed higher IHC score of CD138+ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3+ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Abneg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68+ cells compared to Abneg RA patients not reaching this outcome (p < 0.001).ConclusionsCD117+ and CD138+ cells are differentially distributed among PsA and Abneg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.
Highlights
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by remarkable heterogeneity of clinical presentation, including peripheral arthritis, axial involvement, enthesitis, dactylitis, nail dystrophy, uveitis, and osteitis, in addition to associated comorbidities such as cardiovascular disease, metabolic syndrome, and mood disorders [1, 2]
Each naïve psoriatic arthritis (PsA) and as being seronegative (Abneg) rheumatoid arthritis (RA) patient was treated with methotrexate and followed every 3 months for at least 6 months to assess the rate of achievement of Minimal Disease Activity (MDA) or Disease Activity Score (DAS) remission for PsA and Abneg RA patients respectively
We investigated, for the first time, the synovial histological features of a selected cohort of PsA patients, with peripheral joint involvement, compared to anti-citrullinated peptide antibody (ACPA)/rheumatoid factor (RF) seronegative RA cohort stratified based on the disease phase finding differential histological features of synovial tissue inflammation composition and biomarkers of therapeutic response
Summary
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by remarkable heterogeneity of clinical presentation, including peripheral arthritis, axial involvement, enthesitis, dactylitis, nail dystrophy, uveitis, and osteitis, in addition to associated comorbidities such as cardiovascular disease, metabolic syndrome, and mood disorders [1, 2]. Most patients with PsA present with oligoarticular or polyarticular arthritis and can be differentiated from patients with rheumatoid arthritis (RA), the most common inflammatory joint disease, by specific non-articular clinical features being present, as well as the infrequent seropositivity for rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). These clinical features include an asymmetric distribution of the inflamed joints, the sacroiliitis or spinal involvement, the typical involvement of the distal interphalangeal joint (DIP), and the extra-articular manifestations [1]. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response
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